Arteriolar spasm and ischemia in the ocular fundus of NaCl-loaded salt sensitive Dahl rats: vascular protection by long-term treatment with the calcium antagonist nitrendipine.
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Animals↗
Biomedical subjects
M Frey
Publications and source records attributed to M Frey.
Time course of histomorphometric alterations in nerve grafts without connection to a muscle target organ: an experimental study in sheep.
In 15 adult sheep, the saphenous nerve (28 +/- 1.8 cm) was used for ipsilateral or for cross-nerve grafting and was sutured to the proximal stump of the cut, motor-nerve branch of the vastus muscle. The distal end of the nerve graft was left without a target organ. Semi-thin cross sections of normal vastus nerves and saphenous grafts and of the distal ends of the grafts were analyzed by computer-assisted planimetry, 3, 6, 9, 12, and 18 months after the nerve-grafting procedure. Electronmicroscopy was also performed on specimens from the distal ends of the nerve grafts. Comparing the total number of myelinated nerve fibers in the distal end of the graft, the ipsilateral group showed an increase with time elapsed since nerve grafting, while the cross-over group showed a maximum after 3 and 6 months, and fewer fibers after longer periods of regeneration. Independent of the time passed since nerve grafting, the diameters of the myelinated nerve fibers were homogeneously thin in both experimental groups. Most interesting, the cross-nerve grafts did more poorly than the ipsilateral ones, even before they were influenced by the target muscle. With ultrastructural investigation, the ends of the grafts containing only a few myelinated fibers also showed a low number of unmyelinated fibers, but an increase of collagen fibers. The results have consequences for the clinical application of cross-nerve grafting.
Animals↗
Calcium overload--an important cellular mechanism in hypertension and arteriosclerosis.
Arterial hypertension and arteriosclerosis are dramatic consequences of vascular calcium overload. Acute intracellular calcium overload of vascular smooth muscle cells produces hypercontractility. Hypertension develops if a general increase in systemic arteriolar tone leads to a rise in peripheral flow resistance. Moreover, progressive elevation of calcium destroys the structural integrity of the arterial and arteriolar walls. Thus, in various animals models, calcium overload initiates lesions of an arteriosclerotic character. Interestingly, conventional human coronary plaques also represent a calcium-dominated type of arteriosclerosis. With the advent of specific calcium antagonists, the pathogenic effects of calcium overload and its deleterious consequences have become, for the first time, accessible to therapeutic intervention. Accordingly, adequate treatment with calcium antagonists prevents calcium overload and can thereby protect arteries and arterioles from functional disturbances and structural damage. In spontaneously hypertensive rats, specific calcium antagonists of the verapamil, nifedipine and diltiazem type normalise blood pressure (BP) by reducing transmembrane calcium influx into vascular smooth muscle cells. However, in addition to controlling BP, these drugs also act as tissue protective agents. The long term effects of calcium antagonists such as verapamil in experimental hypertension include the prevention of severe arteriosclerosis, myocardial hypertrophy, and malignant nephrosclerosis. In humans, the antihypertensive efficacy of verapamil is well documented. Further clinical studies have yet to evaluate the antiarteriosclerotic and tissue protective potential of verapamil in humans.
Animals↗
Protective effects of various calcium antagonists against experimental arteriosclerosis.
Arterial walls altered by sclerotic processes accumulate lipids (particularly cholesterol) and calcium. Whereas the accumulation of lipids has long been incriminated as the major pathogenic factor involved in arteriosclerosis, concomitant arterial calcium overload has been considered of secondary importance. Using various animal models and specific calcium antagonists as experimental tools, we have shown the crucial role of excessive calcium uptake into arterial walls in the pathogenesis of arteriosclerotic lesions. Anticalcinotic vasoprotection with calcium antagonists has been demonstrated using light and electron microscopy, radiocalcium uptake experiments and calcium analyses with atomic absorption spectroscopy. The new 1,4-dihydropyridine calcium antagonist amlodipine has been shown to inhibit calcium accumulation in the internal elastic membrane of abdominal arteries of NaCl-loaded salt-sensitive Dahl-S rats, and consequently also exerts protective effects against arteriosclerotic lesions, shown particularly in the distal mesenteric artery branches. Formation of human coronary plaques is marked by a substantial local uptake of calcium, whereas there is a large overlap in the mural cholesterol content of healthy coronary arteries and plaques. Experimental findings in animals and with human tissue indicate that calcium antagonists such as amlodipine may provide a new approach to the prophylaxis of coronary artery lesions.
Amlodipine↗
[Muscle training techniques and retropatellar chondropathy].
The authors have studied the efficacy of 3 different muscle training programs (electromyostimulation, isokinetic training and isometric training) in cases of patellar chondromalacia. The evaluation of the results was made by measuring the isokinetic strength on a Cybex II+ dynamometer at a low (30 degrees/sec) and a high (300 degrees/sec) angular velocity. The clinical evaluation was based on a modified score determined by the Arpege group. The results showed a better improvement of the muscular strength after electromyostimulation or isokinetic training. The clinical improvement was better on patients of groups I and III.
Cartilage Diseases↗
Crystals of Anabaena PCC 7119 ferredoxin-NADP+ reductase.
Crystals of ferredoxin-NADP+ reductase (FNR) from the cyanobacterium Anabaena PCC 7119 are grown in the presence of polyethylene glycol 6000 and beta-octyl glucoside. They belong to the hexagonal system. The cell parameters are a = b = 87.8 A, c = 92.7 A, space group P6(1) or P6(5), and a Vm of 3.0 A3/dalton for one molecule of 36,000 daltons per asymmetric unit. These crystals diffract strongly up to 1.9 A and are suitable for X-ray structural studies.
Crystallization↗
Amino acid sequence and molecular modelling of a thermostable two (4Fe-4S) ferredoxin from the archaebacterium Methanococcus thermolithotrophicus.
The amino acid sequence of a two (4Fe-4S) ferredoxin from the methanogenic bacterium Methanococcus thermolithotrophicus (FdMt) has been determined. This thermostable protein comprises 60 amino acid residues (Mr 6541) and two (4Fe-4S) clusters chelated to the protein through the eight cysteines. FdMt contains a relatively high number of lysines [5], threonines [4] and valines [10]. The three-dimensional molecular model generated from the Peptococcus aerogenes X-ray structure keeps the characteristic overall ferredoxin folding thanks to complementary substitutions of residues of the hydrophobic core. The major structural features of the model are the different environments of both clusters, and the patch of three lysines at one end of the molecule. The possible role of several structural factors in the thermostability of the protein is discussed.
Amino Acid Sequence↗
SDS-soluble and peptidoglycan-bound proteins in the outer membrane-peptidoglycan complex of Brucella abortus.
Outer membrane-peptidoglycan complex from Brucella abortus was separated from cytoplasmic membrane and cytosol by either sucrose density gradient fractionation or differential (rate) centrifugation of surface labeled cells disrupted by sonication without the use of detergents. The outer membrane-peptidoglycan complex had a buoyant density of 1.22 gm/ml and contained 67 labeled SDS-soluble proteins when examined by SDS-PAGE. Included were four major bands exhibiting molecular masses of 88k, 40k, 35.7k and 26k daltons corresponding to previously described group 1, 2 and 3 outer membrane proteins. Lysozyme treatment of outer membrane-peptidoglycan complex increased its buoyant density to 1.25 gm/ml and released eight additional peptidoglycan-linked proteins.
Animals↗
Eukaryotic transposable elements with short terminal inverted repeats.
Transposable elements with short terminal inverted repeats are believed to transpose directly from DNA to DNA via excision and integration. The cis/trans requirements for transposition have recently been characterized for some of these elements. Common features seem to emerge for the mechanisms of excision of these elements, with the mechanisms apparently similar for the different elements.
Animals↗
Histomorphometric studies in patients with facial palsy treated by functional muscle transplantation: new aspects for the surgical concept.
Whenever it was possible, muscle and nerve biopsies were performed in patients with irreversible, unilateral facial palsy treated by cross-face nerve grafting and free gracilis muscle transplantation with microneurovascular anastomoses. Planimetric analyses of cross-sections showed the following, to some extent, surprising, results: (1) Independent of the final functional result, approximately the same number of regenerated, thin nerve fibers (100-200) were found in the distal end of the cross-face nerve graft at the time of muscle transplantation. These are approximately 20% of the nerve fibers counted in the branches of the facial nerve at the healthy side used for reinnervation. (2) There is no correlation between the number or diameter of the nerve fibers in the distal end of the cross-face nerve graft and the functional recovery of the transplanted muscle, but there is good correlation between the morphology of the fibers of the muscle graft and the functional result. (3) Different portions of slow-contracting and fast-contracting muscle fibers in the reinnervated muscle grafts showed the strong influence of the quality of the nerve used for the crossover innervation. If a facial nerve branch innervating the slow buccinator muscle was used, the originally fast gracilis muscle was transformed to a slow muscle by this kind of reinnervation. These important findings are the basis of a new view of surgery in the treatment of irreversible facial palsy by functional free-muscle transplantation.
Biopsy↗
Free muscle transplantation for treatment of facial paralysis: first experiences with the International Muscle Transplant Registry.
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Facial Paralysis↗
First experimental application of multichannel stimulation devices for cardiomyoplasty.
The effect of long-term application of epineural electrodes to nerves was investigated in rat experiments. Neural damage reached a maximum of 6% shortly after implantation and decreased to 3% after 1 year. Impedance and threshold of epineural electrode were investigated in sheep experiments for up to 12 months. The mean impedance was in the range of 1 kohm, while the threshold less than 1 mA. The reduction in fatigue produced by multichannel stimulation was demonstrated by sequential isometric contractions of rectus muscles in sheep. The decrease in force was only 10% after 60 minutes of multichannel stimulation as compared to a reduction of 50% for single channel stimulation. Studies of cardiomyoplasty with single channel stimulation confirmed results reported by other investigators. In acute experiments with sheep, we demonstrated fiber-selective stimulation which led to isolated contraction of the left or right distal part or the right proximal part of the latissimus dorsi muscle. Potential advantages in the application of implantable multichannel stimulation devices as compared to single channel stimulation for cardiomyoplasty include: (1) fatigue-free stimulation at submaximal force level; (2) selection of hemodynamically effective electrode combinations; (3) potential for consecutive activation of muscle fiber groups, thereby allowing better simulation of the physiological contraction of the heart muscle; (4) redundancy of electrodes in case of technical failure or dislocation; and (5) stimulation of more than one muscle, if necessary.
Animals↗
Clarification of ascites fluid.
An essential first step in the purification of monoclonal antibodies is the clarification of the ascites fluid. While not ignored, this step has not received critical attention. Six different procedures were evaluated with respect to effectiveness and impact on several selected chemical components. For large-scale work, we find an on-line filtration process to be most efficient.
Animals↗
The Minnesota Child Development Inventory: validity and reliability for assessing development in infancy.
The concurrent validity and reliability of the Minnesota Child Development Inventory (MCDI) was assessed by comparing the MCDI general development index score, and each of the seven subscale scores, with the mental and psychomotor age equivalents achieved on the Bayley Scales of Infant Development. In addition, the co-positivity, co-negativity, positive and negative predictive values of the MCDI in identifying infants with a mental development index (MDI), or psychomotor development index (PDI) of greater than 2 SD below the mean were assessed. Subjects were 101 infants (8 to 19 months old) who were seen at a neonatal developmental follow-up clinic after discharge from the neonatal intensive care unit. Correlations were obtained for the entire sample as well as for the two chronological age groups (i.e., 8 to 10 months and 17 to 19 months) within the sample. A strong correlation between the MCDI scales and the Bayley Mental and Psychomotor Scales was documented for the entire population as well as for the individual age groups. The overall validity of the MCDI in identifying infants with a MDI or PDI of greater than 2 SD below the mean was limited due to relatively poor co-positivity and positive predictive value. Although the MCDI may yield consistent information about the development of an infant's skills, this research suggests the MCDI has limited capacity to discern infants having delayed development.
Aptitude↗
Differentiation between calcium- and cholesterol-dominated types of arteriosclerotic lesions: antiarteriosclerotic aspects of calcium antagonists.
In a series of animal studies we have clearly demonstrated since 1970 that calcium overload of the arterial wall is crucially involved in the pathogenesis of arteriosclerotic lesions. Following excessive calcium uptake, vascular stretch compliance and distensibility were lost together with structural integrity. Conversely, calcium antagonists that counteract abundant calcium uptake were found to prevent pathogenic mural calcium accumulation and damage. These effects were realized with light and electron microscopy as well as with measurements of calcium accumulation using atomic absorption spectrometry and radiocalcium. The experiments were carried out on rats exposed to various well-known risk factors such as nicotine, alloxan diabetes, high doses of vitamin D3, or dihydrotachysterol. Another particularly vasotoxic factor appeared to be hypertension, which develops in spontaneously hypertensive Okamoto rats (SHRs), in hypertensive NaCl-loaded salt-sensitive Dahl-S rats, and in rats with nephrogenic Goldblatt hypertension. Interestingly, aging arteries in animals and humans also exhibit, as a characteristic phenomenon, a steady increase in arterial calcium content. This natural age-dependent calcium accumulation is further enhanced in severe diabetics, heavy smokers, and hypertensive patients. However, the most excessive degree of toxic calcium overload, correlated with dramatic structural damage, occurred in human coronary artery plaques. Here, in "fatty streaks" (type I plaques according to World Health Organization classification), the mural calcium content exhibited a rise by 13 times above normal; in type II lesions (fibrous plaques), the increase in calcium was 24-fold; and in type III plaques, i.e., in "complicated lesions of stenosing character," calcium overload amounted to a value greater than 80 times above that found in healthy coronary segments.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
[A differential diagnosis of quadricipital amyotrophy syndrome: bilateral disinsertion of the quadriceps tendon].
When it occurs bilaterally, disinsertion of the quadriceps tendons may suggest quadricipital amyotrophy syndrome. Questioning and physical examination of the locomotor system usually lead to a diagnosis of mechanical lesion involving the extensor mechanism of the knee. If necessary, this diagnosis can be confirmed by ultrasonography and MRI of the knee. A search for predisposing factors may result in a specific treatment, but only surgery provides functional improvement.
Aged↗
X-ray crystal structure determination and refinement at 1.9 A resolution of isolectin I from the seeds of Lathyrus ochrus.
Orthorhombic crystals of isolectin I (LOLI) from the seeds of Lathyrus ochrus were first obtained during the STS 29 space shuttle mission. Subsequently, isostructural crystals were also obtained in the laboratory. They belong to the space group P2(1)2(1)2, with cell dimensions a = 135.84 A, b = 63.12 A and c = 54.54 A with one functional entity, a dimer, in the asymmetric unit (Vm = 2.2 A3/Da). The three-dimensional structure of LOLI, which was solved by the molecular replacement method using a 3 A resolution model of pea lectin, has subsequently been refined by using crystallographic data between 8.0 A and 1.9 A resolution, coupled to molecular dynamics and energy minimization techniques. The conventional R-factor is 0.185 for Fo greater than 1 sigma(Fo). The final model includes 220 well-defined water molecules and has root-mean-square deviations from ideal bond distances and angles of 0.004 A and 3 degrees, respectively. Only slight conformation differences have been found between the two alpha beta monomers. The molecular structure of LOLI, the first to be determined from the genus Lathyrus, is very similar to those of concanavalin A, pea lectin and favin. Differences are confined to the loop regions and beta-chain termini. Comparison of equivalent C alpha atom positions between our final model and the pea lectin structure shows slight differences in the association of the two monomers, which are probably due to the different environments in the crystals. The root-mean-square deviation between C alpha atoms of LOLI and pea lectin is 0.40 A. The metal binding sites are very similar in pea lectin, concanavalin A and LOLI. The sugar-binding sites of LOLI are occupied by four well-ordered water molecules each. The cleavage site for one of the monomers is specially well defined in the final electron density map: the amino group of Glul (alpha) seems to form a salt bridge with the carboxylate group of the terminal Asn181 (beta). A detailed analysis of the difference in crystal packing contacts between pea lectin and LOLI shows that, as might be expected, several of the intermolecular interactions are mediated by residues that correspond to substitutions in the LOLI amino acid sequence.
Amino Acid Sequence↗
Excision of the En/Spm transposable element of Zea mays requires two element-encoded proteins.
An excision assay system for En/Spm was developed in transgenic tobacco. The characteristics of excision and integration are similar to the natural system of Zea mays. In this transgenic model system two En/Spm encoded trans-acting functions, TNPA and TNPD, are required for excision. A biochemical model for transposition is proposed that might also be applicable to other transposable elements.
Cloning, Molecular↗